title: FMRI and fcMRI phenotypes map the genomic effect of chromosome 13 in Brown Norway and Dahl salt-sensitive rats.
abstract: Genes have been implicated as major contributors to many biological traits and susceptibility to specific diseases. However, the mechanisms of genotype action on central nervous system function have been elusive. It has been previously observed that inbred Brown Norway (BN) rats exhibit a number of quantitative complex traits markedly different from those of inbred Dahl salt-sensitive (SS) rats. These strains have become so important to cardiovascular research that a novel chromosome substitution approach was used to create SS and BN strains that have a single chromosome replaced by the homologous chromosome of the other strain. The present study was conducted in an effort to evaluate whether fMRI neuroimaging measures could be employed as a phenotype of genetic influence on neural biology in SS, BN, and consomic SSBN13 rat strains. Electrical forepaw stimulation evoked robust differential BOLD-fMRI activation along the thalamocortical pathway among the three strains across different stimulus frequencies. Moreover, using the fMRI-guided seeds in thalamus and somatosensory cortex for the analysis of fcMRI, we were able to characterize the strain-specific difference in secondary somatosensory cortex, temporal association cortex, and the CA3 region. We were also able to define the genetic influences of Chr-13 on the projection and integration of sensory information in consomic SS-13(BN) strain. We provided objective imaging evidence supporting the hypothesis that rat strain-specific fMRI and fcMRI combined with consomic strategy can be a useful tool in identifying the complex genetic divergence that is related to neural circuits. These findings prove the concept of neuroimaging-based phenotypes as a novel approach to visualize and fine-map the genetic effects onto brain biology at a systems level.
authors.affiliation: Department of Plastic Surgery, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: B Douglas
authors.initials: BD
authors.lastname: Ward
authors.affiliation: Department of Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Melinda R
authors.initials: MR
authors.lastname: Dwinell
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Julian H
authors.initials: JH
authors.lastname: Lombard
authors.affiliation: Department of Plastic Surgery, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: cpawela@mcw.com.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Pawela
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D001931:Brain Mapping; D033481:Chromosomes, Mammalian / Q000235:genetics*; D004558:Electric Stimulation; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000502:physiology*; D010641:Phenotype; D040641:Quantitative Trait Loci; D051381:Rats / Q000235:genetics; D011914:Rats, Inbred BN / Q000235:genetics*; D020303:Rats, Inbred Dahl / Q000235:genetics*
keywords: Brain; Chromosome; Functional MRI; Functional connectivity; Imaging genetics; MRI resting-state; Phenotype; Rat